Pathways that extend lifespan by 500 percent identified

Caenorhabditis elegans (stock image).

Scientists at the MDI Biological Laboratory, in collaboration with scientists from the Buck Institute for Research on Aging in Novato, Calif., and Nanjing University in China, have identified synergistic cellular pathways for longevity that amplify lifespan fivefold in C. elegans, a nematode worm used as a model in aging research.

The increase in lifespan would be the equivalent of a human living for 400 or 500 years, according to one of the scientists.

The research draws on the discovery of two major pathways governing aging in C. elegans, which is a popular model in aging research because it shares many of its genes with humans and because its short lifespan of only three to four weeks allows scientists to quickly assess the effects of genetic and environmental interventions to extend healthy lifespan.

Because these pathways are "conserved," meaning that they have been passed down to humans through evolution, they have been the subject of intensive research. A number of drugs that extend healthy lifespan by altering these pathways are now under development. The discovery of the synergistic effect opens the door to even more effective anti-aging therapies.

The new research uses a double mutant in which the insulin signaling (IIS) and TOR pathways have been genetically altered. Because alteration of the IIS pathways yields a 100 percent increase in lifespan and alteration of the TOR pathway yields a 30 percent increase, the double mutant would be expected to live 130 percent longer. But instead, its lifespan was amplified by 500 percent.

"Despite the discovery in C. elegans of cellular pathways that govern aging, it hasn't been clear how these pathways interact," said Hermann Haller, M.D., president of the MDI Biological Laboratory. "By helping to characterize these interactions, our scientists are paving the way for much-needed therapies to increase healthy lifespan for a rapidly aging population."

The elucidation of the cellular mechanisms controlling the synergistic response is the subject of a recent paper in the online journal Cell Reports entitled "Translational Regulation of Non-autonomous Mitochondrial Stress Response Promotes Longevity." The authors include Jarod A. Rollins, Ph.D., and Aric N. Rogers, Ph.D., of the MDI Biological Laboratory.

"The synergistic extension is really wild," said Rollins, who is the lead author with Jianfeng Lan, Ph.D., of Nanjing University. "The effect isn't one plus one equals two, it's one plus one equals five. Our findings demonstrate that nothing in nature exists in a vacuum; in order to develop the most effective anti-aging treatments we have to look at longevity networks rather than individual pathways."

The discovery of the synergistic interaction could lead to the use of combination therapies, each affecting a different pathway, to extend healthy human lifespan in the same way that combination therapies are used to treat cancer and HIV, Pankaj Kapahi, Ph.D., of the Buck Institute, has said. Kapahi is a corresponding author of the paper with Rogers and Di Chen, Ph.D., of Nanjing University.

The synergistic interaction may also may explain why scientists have been unable to identify a single gene responsible for the ability of some people to live to extraordinary old ages free of major age-related diseases until shortly before their deaths.

The paper focuses on how longevity is regulated in the mitochondria, which are the organelles in the cell responsible for energy homeostasis. Over the last decade, accumulating evidence has suggested a causative link between mitochondrial dysregulation and aging. Rollins' future research will focus on the further elucidation of the role of mitochondria in aging, he said.

The research was conducted at the MDI Biological Laboratory and Nanjing University using information from double mutants developed by Kapahi. Rollins' and Rogers' work was supported by the National Institutes of Health (AG056743), the Morris Scientific Discovery Fund and the National Institute of General Medical Sciences (P20GM103423 and P20GM104318).

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Materials provided by Mount Desert Island Biological Laboratory. Note: Content may be edited for style and length.

Pathways that extend lifespan by 500 percent identified

Caenorhabditis elegans (stock image).

Scientists at the MDI Biological Laboratory, in collaboration with scientists from the Buck Institute for Research on Aging in Novato, Calif., and Nanjing University in China, have identified synergistic cellular pathways for longevity that amplify lifespan fivefold in C. elegans, a nematode worm used as a model in aging research.

The increase in lifespan would be the equivalent of a human living for 400 or 500 years, according to one of the scientists.

The research draws on the discovery of two major pathways governing aging in C. elegans, which is a popular model in aging research because it shares many of its genes with humans and because its short lifespan of only three to four weeks allows scientists to quickly assess the effects of genetic and environmental interventions to extend healthy lifespan.

Because these pathways are "conserved," meaning that they have been passed down to humans through evolution, they have been the subject of intensive research. A number of drugs that extend healthy lifespan by altering these pathways are now under development. The discovery of the synergistic effect opens the door to even more effective anti-aging therapies.

The new research uses a double mutant in which the insulin signaling (IIS) and TOR pathways have been genetically altered. Because alteration of the IIS pathways yields a 100 percent increase in lifespan and alteration of the TOR pathway yields a 30 percent increase, the double mutant would be expected to live 130 percent longer. But instead, its lifespan was amplified by 500 percent.

"Despite the discovery in C. elegans of cellular pathways that govern aging, it hasn't been clear how these pathways interact," said Hermann Haller, M.D., president of the MDI Biological Laboratory. "By helping to characterize these interactions, our scientists are paving the way for much-needed therapies to increase healthy lifespan for a rapidly aging population."

The elucidation of the cellular mechanisms controlling the synergistic response is the subject of a recent paper in the online journal Cell Reports entitled "Translational Regulation of Non-autonomous Mitochondrial Stress Response Promotes Longevity." The authors include Jarod A. Rollins, Ph.D., and Aric N. Rogers, Ph.D., of the MDI Biological Laboratory.

"The synergistic extension is really wild," said Rollins, who is the lead author with Jianfeng Lan, Ph.D., of Nanjing University. "The effect isn't one plus one equals two, it's one plus one equals five. Our findings demonstrate that nothing in nature exists in a vacuum; in order to develop the most effective anti-aging treatments we have to look at longevity networks rather than individual pathways."

The discovery of the synergistic interaction could lead to the use of combination therapies, each affecting a different pathway, to extend healthy human lifespan in the same way that combination therapies are used to treat cancer and HIV, Pankaj Kapahi, Ph.D., of the Buck Institute, has said. Kapahi is a corresponding author of the paper with Rogers and Di Chen, Ph.D., of Nanjing University.

The synergistic interaction may also may explain why scientists have been unable to identify a single gene responsible for the ability of some people to live to extraordinary old ages free of major age-related diseases until shortly before their deaths.

The paper focuses on how longevity is regulated in the mitochondria, which are the organelles in the cell responsible for energy homeostasis. Over the last decade, accumulating evidence has suggested a causative link between mitochondrial dysregulation and aging. Rollins' future research will focus on the further elucidation of the role of mitochondria in aging, he said.

The research was conducted at the MDI Biological Laboratory and Nanjing University using information from double mutants developed by Kapahi. Rollins' and Rogers' work was supported by the National Institutes of Health (AG056743), the Morris Scientific Discovery Fund and the National Institute of General Medical Sciences (P20GM103423 and P20GM104318).

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Materials provided by Mount Desert Island Biological Laboratory. Note: Content may be edited for style and length.

First identified comet to visit our solar system from another star

Comet 2I/Borisov is only the second interstellar object known to have passed through the solar system. These two images, taken by NASA's Hubble Space Telescope, capture the comet appearing near a background galaxy (left) and soon after its closest approach to the Sun (right).

Credit: NASA, ESA, and D. Jewitt (UCLA)

When astronomers see something in the universe that at first glance seems like one-of-a-kind, it's bound to stir up a lot of excitement and attention. Enter comet 2I/Borisov. This mysterious visitor from the depths of space is the first identified comet to arrive here from another star. We don't know from where or when the comet started heading toward our Sun, but it won't hang around for long. The Sun's gravity is slightly deflecting its trajectory, but can't capture it because of the shape of its orbit and high velocity of about 100,000 miles per hour.

Telescopes around the world have been watching the fleeting visitor. NASA's Hubble Space Telescope has provided the sharpest views as the comet skirts by our Sun. Since October the space telescope has been following the comet like a sports photographer following horses speeding around a racetrack. Hubble revealed that the heart of the comet, a loose agglomeration of ices and dust particles, is likely no more than about 3,200 feet across, about the length of nine football fields. Though comet Borisov is the first of its kind, no doubt there are many other comet vagabonds out there, plying the space between stars. Astronomers will eagerly be on the lookout for the next mysterious visitor from far beyond.

These two images, taken by Hubble, capture comet 2I/Borisov streaking though our solar system and on its way back to interstellar space. It is only the second interstellar object known to have passed through the solar system.

Nov. 16, 2019, photo

The comet appears in front of a distant background spiral galaxy (2MASX J10500165-0152029). The galaxy's bright central core is smeared in the image because Hubble was tracking the comet. Comet Borisov was approximately 203 million miles from Earth in this exposure. Its tail of ejected dust streaks off to the upper right. The comet has been artificially colored blue to discriminate fine detail in the halo of dust, or coma, surrounding the central nucleus. It also helps to visually separate the comet from the background galaxy.

Dec. 9, 2019, photo

Hubble revisited the comet shortly after its closest approach to the Sun where it received maximum heating after spending most of its life in frigid interstellar space. The comet also reached a breathtaking maximum speed of about 100,000 miles per hour. Comet Borisov is 185 million miles from Earth in this photo, near the inner edge of the asteroid belt but below it. The nucleus, an agglomeration of ices and dust, is still too small to be resolved. The bright central portion is a coma made up of dust leaving the surface. The comet will make its closest approach to Earth in late December at a distance of 180 million miles.

"Hubble gives us the best upper limit of the size of comet Borisov's nucleus, which is the really important part of the comet," said David Jewitt, a UCLA professor of planetary science and astronomy, whose team has captured the best and sharpest look at this first confirmed interstellar comet. "Surprisingly, our Hubble images show that its nucleus is more than 15 times smaller than earlier investigations suggested it might be. Our Hubble images show that the radius is smaller than half a kilometer. Knowing the size is potentially useful for beginning to estimate how common such objects may be in the solar system and our galaxy. Borisov is the first known interstellar comet, and we would like to learn how many others there are."

Crimean amateur astronomer Gennady Borisov discovered the comet on Aug. 30, 2019, and reported the position measurements to the International Astronomical Union's Minor Planet Center in Cambridge, Massachusetts. The Center for Near-Earth Object Studies at NASA's Jet Propulsion Laboratory in Pasadena, California, working with the Minor Planet Center, computed an orbit for the comet, which shows that it came from elsewhere in our Milky Way galaxy, point of origin unknown.

Nevertheless, observations by numerous telescopes show that the comet's chemical composition is similar to the comets found inside our solar system, providing evidence that comets also form around other stars. By the middle of 2020 the comet will have already zoomed past Jupiter's distance of 500 million miles on its way back into the frozen abyss of interstellar space.

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Materials provided by NASA/Goddard Space Flight Center. Note: Content may be edited for style and length.

First identified comet to visit our solar system from another star

Comet 2I/Borisov is only the second interstellar object known to have passed through the solar system. These two images, taken by NASA's Hubble Space Telescope, capture the comet appearing near a background galaxy (left) and soon after its closest approach to the Sun (right).

When astronomers see something in the universe that at first glance seems like one-of-a-kind, it's bound to stir up a lot of excitement and attention. Enter comet 2I/Borisov. This mysterious visitor from the depths of space is the first identified comet to arrive here from another star. We don't know from where or when the comet started heading toward our Sun, but it won't hang around for long. The Sun's gravity is slightly deflecting its trajectory, but can't capture it because of the shape of its orbit and high velocity of about 100,000 miles per hour.

Telescopes around the world have been watching the fleeting visitor. NASA's Hubble Space Telescope has provided the sharpest views as the comet skirts by our Sun. Since October the space telescope has been following the comet like a sports photographer following horses speeding around a racetrack. Hubble revealed that the heart of the comet, a loose agglomeration of ices and dust particles, is likely no more than about 3,200 feet across, about the length of nine football fields. Though comet Borisov is the first of its kind, no doubt there are many other comet vagabonds out there, plying the space between stars. Astronomers will eagerly be on the lookout for the next mysterious visitor from far beyond.

These two images, taken by Hubble, capture comet 2I/Borisov streaking though our solar system and on its way back to interstellar space. It is only the second interstellar object known to have passed through the solar system.

Nov. 16, 2019, photo

The comet appears in front of a distant background spiral galaxy (2MASX J10500165-0152029). The galaxy's bright central core is smeared in the image because Hubble was tracking the comet. Comet Borisov was approximately 203 million miles from Earth in this exposure. Its tail of ejected dust streaks off to the upper right. The comet has been artificially colored blue to discriminate fine detail in the halo of dust, or coma, surrounding the central nucleus. It also helps to visually separate the comet from the background galaxy.

Dec. 9, 2019, photo

Hubble revisited the comet shortly after its closest approach to the Sun where it received maximum heating after spending most of its life in frigid interstellar space. The comet also reached a breathtaking maximum speed of about 100,000 miles per hour. Comet Borisov is 185 million miles from Earth in this photo, near the inner edge of the asteroid belt but below it. The nucleus, an agglomeration of ices and dust, is still too small to be resolved. The bright central portion is a coma made up of dust leaving the surface. The comet will make its closest approach to Earth in late December at a distance of 180 million miles.

"Hubble gives us the best upper limit of the size of comet Borisov's nucleus, which is the really important part of the comet," said David Jewitt, a UCLA professor of planetary science and astronomy, whose team has captured the best and sharpest look at this first confirmed interstellar comet. "Surprisingly, our Hubble images show that its nucleus is more than 15 times smaller than earlier investigations suggested it might be. Our Hubble images show that the radius is smaller than half a kilometer. Knowing the size is potentially useful for beginning to estimate how common such objects may be in the solar system and our galaxy. Borisov is the first known interstellar comet, and we would like to learn how many others there are."

Crimean amateur astronomer Gennady Borisov discovered the comet on Aug. 30, 2019, and reported the position measurements to the International Astronomical Union's Minor Planet Center in Cambridge, Massachusetts. The Center for Near-Earth Object Studies at NASA's Jet Propulsion Laboratory in Pasadena, California, working with the Minor Planet Center, computed an orbit for the comet, which shows that it came from elsewhere in our Milky Way galaxy, point of origin unknown.

Nevertheless, observations by numerous telescopes show that the comet's chemical composition is similar to the comets found inside our solar system, providing evidence that comets also form around other stars. By the middle of 2020 the comet will have already zoomed past Jupiter's distance of 500 million miles on its way back into the frozen abyss of interstellar space.

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Materials provided by NASA/Goddard Space Flight Center. Note: Content may be edited for style and length.

Specific neurons that map memories now identified in the human brain

An important aspect of human memory is our ability to conjure specific moments from the vast array of experiences that have occurred in any given setting. For example, if asked to recommend a tourist itinerary for a city you have visited many times, your brain somehow enables you to selectively recall and distinguish specific memories from your different trips to provide an answer.

Studies have shown that declarative memory -- the kind of memory you can consciously recall like your home address or your mother's name -- relies on healthy medial temporal lobe structures in the brain, including the hippocampus and entorhinal cortex (EC). These regions are also important for spatial cognition, demonstrated? by the Nobel-Prize-winning discovery of "place cells" and "grid cells" in these regions -- neurons that activate to represent specific locations in the environment during navigation (akin to a GPS). However, it has not been clear if or how this "spatial map" in the brain relates to a person's memory of events at those locations, and how neuronal activity in these regions enables us to target a particular memory for retrieval among related experiences.

A team led by neuroengineers at Columbia Engineering has found the first evidence that individual neurons in the human brain target specific memories during recall. They studied recordings in neurosurgical patients who had electrodes implanted in their brains and examined how the patients' brain signals corresponded to their behavior while performing a virtual-reality (VR) object-location memory task. The researchers identified "memory-trace cells" whose activity was spatially tuned to the location where subjects remembered encountering specific objects. The study is published today in Nature Neuroscience.

"We found these memory-trace neurons primarily in the entorhinal cortex (EC), which is one of the first regions of the brain affected by the onset of Alzheimer 's disease," says Joshua Jacobs, associate professor of biomedical engineering, who directed the study. "Because the activity of these neurons is closely related to what a person is trying to remember, it is possible that their activity is disrupted by diseases like Alzheimer's, leading to memory deficits. Our findings should open up new lines of investigation into how neural activity in the entorhinal cortex and medial temporal lobe helps us target past events for recall, and more generally how space and memory overlap in the brain."

The team was able to measure the activity of single neurons by taking advantage of a rare opportunity: invasively recording from the brains of 19 neurosurgical patients at several hospitals, including the Columbia University Irving Medical Center. The patients had drug-resistant epilepsy and so had already had recording electrodes implanted in their brains for their clinical treatment. The researchers designed experiments as engaging and immersive VR computer games and the bedridden patients used laptops and handheld controllers to move through virtual environments. In performing the task, subjects first navigated through the environment to learn the locations of four unique objects. Then the researchers removed the objects and asked patients to move through the environment and mark the location of one specific object on each trial.

The team measured the activity of neurons as the patients moved through the environment and marked their memory targets. Initially, they identified purely spatially tuned neurons similar to "place cells" that always activated when patients moved through specific locations, regardless of the subjects' memory target. "These neurons seemed only to care about the person's spatial location, like a pure GPS," says Salman E. Qasim, Jacobs' PhD student and lead author of the study.

But the researchers also noticed that other neurons only activated in locations relevant to the memory the patient was recalling on that trial -- whenever patients were instructed to target a different memory for recall, these neurons changed their activity to match the new target's remembered location. What especially excited Jacobs and Qasim is that they could actually decode the specific memory a patient was targeting based on the activity of these neurons.

"Our study demonstrates that neurons in the human brain track the experiences we are willfully recalling, and can change their activity patterns to differentiate between memories. They're just like the pins on your Google map that mark the locations you remember for important events," Qasim says. "This discovery might provide a potential mechanism for our ability to selectively call upon different experiences from the past and highlights how these memories may influence our brain's spatial map."

Jacobs and Qasim plan next to look for evidence that these neurons represent memories in non-spatial contexts to better characterize their role in memory function. "We know now that neurons care about where our memories occur and now we want to see if these neurons care about other features of those memories, like when they occurred, what occurred, and so on," Qasim notes.

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Materials provided by Columbia University School of Engineering and Applied Science. Original written by Holly Evarts.